We are in the fourth and final year of a study of the relationship between human immunodeficiency virus (HIV), and types of human papillomavirus (HPV), immunosuppression, and risk of development of high grade anal squamous intraepithelial lesions (HGASIL), the anal cancer precursor lesion most closely related to invasive anal cancer (R01CA55488, Nancy Kiviat PI). Our major findings included: a) development of high grade anal squamous intraepithelial lesions (HGASIL) is associated with HIV seropositivity, with HIV seropositive men with CD4 count below 500/mul at greatest risk; b) among both HIV seropositive and HIV seronegative men, development of HGASIL associated with high levels of HPV types 16/18; (c) development of HGASIL is associated with low risk HPV type HPV in addition to HPV 16/18 among HIV seropositive, but not among seronegative men; and d) HIV seronegative were much more likely to regress from HGASIL to normal than were HIV seropositive men. We now propose a survey of questions focused on further exploring the relationship between HIV and HPV. We will: 1) test the hypothesis that the development of ASIL is associated with the presence and amount of HIV; 2) determine whether there is support of the hypothesis that the effect of anal HIV on anal HPV is (a) the result of local HIV induced immunosuppression (b) direct effect of HIV on HPV; and 3) initiate studies examining the characteristics, pathogenesis and clinical consequences of anal HIV variants: by cross sectional analysis of first visit samples. In summary, we propose a survey of questions that are likely to contribute significantly to our understanding of both general HIV pathogenesis and the development of HPV-related pathology among HIV-seropositive men.